Negative cross-talk between the human orphan nuclear receptor Nur77/NAK-1/TR3 and nuclear factor-kappaB

Nucleic Acids Res. 2004 Oct 5;32(17):5280-90. doi: 10.1093/nar/gkh856. Print 2004.


The effect of orphan nuclear receptor Nur77 overexpression on activation of an interleukin-2 (IL-2) promoter-luciferase construct was analyzed in the human leukemic cell line Jurkat. Cotransfection of the IL-2 promoter construct together with the Nur77 expression plasmid resulted in a significant repression of IL-2 promoter activation compared to control cells. The repression by Nur77 requires the N-terminal activation function-1 domain. The repressive effect of Nur77 on IL-2 promoter activation is mediated through inhibition of the transcription factor complex nuclear factor-kappaB (NF-kappaB), since blocking or alteration of the IL-2 NF-kappaB binding sites resulted in abrogation of the repressive effect of Nur77. Moreover, further examination of a reporter gene construct containing multiple copies of the IL-2 CD28 response element (CD28RE) showed that Nur77 can inhibit transactivation mediated by the NF-kappaB components p65 and c-Rel. However, no effect of Nur77 was seen on p65-mediated transactivation of a construct containing multiple NF-kappaB binding sites of the HIV LTR. Our data suggest that Nur77 is able to block activation through NF-kappaB when bound to low-affinity NF-kappaB binding sites, such as those located in the IL-2 promoter.

MeSH terms

  • Amino Acid Sequence
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism*
  • Down-Regulation
  • Gene Expression Regulation*
  • Humans
  • Interleukin-2 / genetics
  • Jurkat Cells
  • NF-kappa B / metabolism*
  • Nuclear Receptor Subfamily 4, Group A, Member 1
  • Promoter Regions, Genetic
  • Protein Structure, Tertiary
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Steroid
  • Repressor Proteins / chemistry
  • Repressor Proteins / metabolism*
  • Signal Transduction
  • Transcription Factors / chemistry
  • Transcription Factors / metabolism*
  • Transcriptional Activation


  • DNA-Binding Proteins
  • Interleukin-2
  • NF-kappa B
  • NR4A1 protein, human
  • Nuclear Receptor Subfamily 4, Group A, Member 1
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Steroid
  • Repressor Proteins
  • Transcription Factors